Michael J. Quinn

Sentinel lymph node status as an indicator of the presence of metastatic melanoma in regional lymph nodes

The value of elective lymph node dissection (ELND) for melanoma patients with clinically uninvolved regional nodes remains controversial. However, it has been proposed that selective sentinel lymph node biopsy reliably identifies individuals with micrometastases, who are most likely to benefit from full ELND. The aim of this study was to confirm that metastatic melanoma cells travelling in lymphatics do not bypass the sentinel node. After preoperative lymphoscintigraphy and intraoperative injection of blue dye around the primary melanoma site, sentinel node biopsy was performed in 118 melanoma patients for whom full ELND was planned as part of their definitive surgical treatment. A confidently identified sentinel node was tumour positive in 22 out of 105 regional lymph node fields (21%). In 18 cases the sentinel node was the only node found to be involved and in four cases, additional nodes were positive. In two other patients a positive node was found when the sentinel lymph node had been negative. However, in each case an avoidable error of technique had occurred and definite blue staining indicated that the positive node was in fact another sentinel node. This study thus confirms that sentinel lymph node status reliably indicates whether metastatic melanoma is present in regional lymph nodes.

Prediction of potential metastatic sites in cutaneous head and neck melanoma using lymphoscintigraphy

BACKGROUNDnThe technique of lymphoscintigraphy may allow a more selective approach to the management of clinically negative neck nodes among patients with cutaneous head and neck melanoma.nnnPATIENTS AND METHODSnA group of 97 patients with cutaneous head and neck melanoma had preoperative lymphoscintigraphy using intradermal injections of technetium 99m antimony trisulfide colloid to identify sentinel nodes. Fifty-one patients were eligible for clinical analysis after initial definitive treatment by wide excision only (n = 11), wide excision and elective dissection of the neck (n = 19) or axilla (n = 1), or wide excision and a sentinel node biopsy procedure (n = 20).nnnRESULTSnSentinel nodes were identified in 95 of 97 lymphoscintigrams, and 85% of patients had multiple sentinel nodes. In 21 patients (22%), sentinel nodes were identified outside the parotid region and the 5 main neck levels, mostly in postauricular nodes (n = 13). Lymphoscintigrams were discordant with clinical predictions in 33 patients (34%). Lymph nodes were positive in 4 elective dissections and 4 sentinel node biopsies. Among 16 patients evaluable after wide excision and a negative sentinel node biopsy, 4 patients subsequently developed metastatic nodes; however, confident identification of all nodes marked as sentinel nodes on lymphoscintigraphy was not achieved at the original biopsy procedure in 3 of these patients.nnnCONCLUSIONSnLymphoscintigraphy and sentinel node biopsy are more difficult to perform in the head and neck than in other parts of the body. The reliability of sentinel node biopsy based on lymphoscintigraphy may be improved by identifying and marking all nodes that are considered to receive direct lymphatic drainage from the primary melanoma, and by use of a gamma probe intraoperatively.

Location of sentinel lymph nodes in patients with cutaneous melanoma: new insights into lymphatic anatomy

BACKGROUNDnAccurate staging of melanoma patients by sentinel node (SN) biopsy can be achieved only if all SNs draining a given melanoma site are identified and removed for detailed histologic examination. Lymphoscintigraphy with a radiolabeled colloid provides an objective and reliable method of locating SNs and demonstrates that confident prediction of their location is not possible on clinical grounds.nnnSTUDY DESIGNnLymphatic drainage pathways demonstrated by preoperative lymphoscintigraphy for 1,759 patients with primary cutaneous melanomas were reviewed, and locations of SNs in these patients were documented. An SN was defined as any node receiving direct lymphatic drainage from a primary melanoma site.nnnRESULTSnIn many instances the cutaneous lymphatic drainage pathways were found to be at variance with longheld concepts of lymphatic anatomy. Several new pathways were identified, draining to SNs in unexpected sites. These included triangular intermuscular space SNs (from upper back and, rarely, upper limb primaries), paraaortic and retroperitoneal SNs (from upper and lower back primaries), and costal margin SNs with onward drainage to internal mammary nodes (from periumbilical primaries). Occasional drainage to node fields on the opposite side of the body was noted from head, neck, and trunk primaries, and drainage to interval nodes (by definition, SNs) outside recognized lymph node fields was also observed.nnnCONCLUSIONSnKnowledge of the possibility of these unusual lymphatic drainage patterns and SN sites should help to ensure the accuracy and completeness of SN identification. Preoperative lymphoscintigraphy to definitively locate SNs is recommended for every patient undergoing an SN biopsy procedure.

Lymphoscintigraphy to identify sentinel lymph nodes in patients with melanoma.

Lymphoscintigraphy (LS) has been performed for 8 years in patients of the Sydney Melanoma Unit, to define lymphatic drainage patterns. Over the past 2 years, LS has also been used to locate the sentinel lymph node prior to surgery. Our technique for LS and subsequent sentinel node biopsy has an accuracy of 97%. All sentinel nodes must be marked to ensure the successful application of the sentinel biopsy technique. We have found that the axilla and groin average just over one sentinel node per draining node group for lesions on the trunk and upper limb, but have noted that drainage to the groin differed when lower limb lesions were studied. Because of the anastomosis of lymph vessels in the upper thigh, multiple sentinel nodes are identified in the groin in some patients. We have found an average of three sentinel nodes in the groin when lymph drainage from lower limb lesions was studied with LS. This difference demands a modification of the LS technique, with early imaging of the groin nodes to identify all sentinel nodes in each patient. The depth of the sentinel nodes can also be measured and the location of all interval nodes marked on the skin. This ensures that all sentinel nodes and interval nodes can be removed at the time of surgery.

Outcome in 846 Cutaneous Melanoma Patients From a Single Center After a Negative Sentinel Node Biopsy

BackgroundA negative sentinel node biopsy (SNB) implies a good prognosis for melanoma patients. The purpose of this study was to determine the long-term outcome for melanoma patients with a negative SNB.MethodsSurvival and prognostic factors were analyzed for 836 SNB-negative patients. All patients with a node field recurrence were reviewed, and sentinel node (SN) tissue was reexamined.ResultsThe median tumor thickness was 1.7 mm, and 23.8% were ulcerated. The median follow-up was 42.1 months. Melanoma specific survival at 5 years was 90%, compared with 56% for SN-positive patients (P < .001). On multivariate analysis, only thickness and ulceration retained significance for disease-free and disease-specific survival. Five-year survival for patients with nonulcerated lesions was 94% vs. 78% with ulceration. Eighty-three patients (9.9%) had a recurrence. Twenty-seven patients developed recurrence in the regional node field, and in 22 of these, it was the first recurrence site. Six developed local recurrence, 17 an in-transit metastasis, and 58 distant disease. The false-negative rate was 13.2%. SN slides and tissue blocks were further examined in 18 patients with recurrence in the node field, and metastatic disease was found in 3 of them.ConclusionsThis large, single-center study confirms that patients with a negative SNB have a significantly better prognosis than those with positive SNs. In those with a negative SNB, primary tumor thickness and ulceration are independent predictors of survival. Incorrect pathologic diagnosis contributed to only a minority of the false-negative results in this study.

Correlation between preoperative lymphoscintigraphy and metastatic nodal disease sites in 362 patients with cutaneous melanomas of the head and neck.

Objective:Lymphoscintigraphy for head and neck melanomas demonstrates a wide variation in lymphatic drainage pathways, and sentinel nodes (SNs) are reported in sites that are not clinically predicted (discordant). To assess the clinical relevance of these discordant node fields, the lymphoscintigrams of patients with head and neck melanomas were analyzed and correlated with the sites of metastatic nodal disease. Methods:In 362 patients with head and neck melanomas who underwent lymphoscintigraphy, the locations of the SNs were compared with the locations of the primary tumors. The SNs were removed and examined in 136 patients and an elective or therapeutic regional lymph node dissection was performed in 40 patients. Results:Lymphoscintigraphy identified a total of 918 SNs (mean 2.5 per patient). One or more SNs was located in a discordant site in 114 patients (31.5%). Lymph node metastases developed in 16 patients with nonoperated SNs, all underneath the tattoo spots on the skin used to mark the position of the SNs. In 14 patients SN biopsy revealed metastatic melanoma. After a negative SN biopsy procedure 11 patients developed regional lymph node metastases during follow-up. Elective and therapeutic neck dissections demonstrated 10 patients with nodal metastases, all located in predicted node fields. Of the 51 patients with involved lymph nodes, 7 had positive nodes in discordant sites (13.7%). Conclusions:Metastases from head and neck melanomas can occur in any SN demonstrated by lymphoscintigraphy. SNs in discordant as well as predicted node fields should be removed and examined to optimize the accuracy of staging.

Treatment of metastatic melanoma using electroporation therapy with bleomycin (electrochemotherapy).

Electroporation therapy (EPT) is a novel treatment modality that uses brief, high-intensity, pulsed electrical currents to enhance the uptake of chemotherapeutic agents, vaccines and genes into cells. This technique is potentially useful for patients with secondary and, possibly, some primary tumours. Nineteen patients with metastatic melanoma were enrolled in a phase two, randomized, open-label study comparing intralesional bleomycin+EPT with intralesional bleomycin alone. Of 18 study lesions, 13 (72%) showed a complete response, one (5%) showed a partial response, three (18%) showed no change and one (5%) showed disease progression over a period of greater than 12u2009weeks. This represents a 78% objective response rate, which was significantly greater than the 32% response rate observed in the 19 patients with tumours treated with intralesional bleomycin alone (χ2=7.94, 1 df, P=0.005). An additional 36 lesions, not enrolled in the study, were also treated with bleomycin+EPT. Of the total of 54 lesions treated with bleomycin+EPT, there was a 72% objective response rate. EPT treatment was well tolerated and was performed on an outpatient basis.

Subungual Melanoma: A Study of 124 Cases Highlighting Features of Early Lesions, Potential Pitfalls in Diagnosis, and Guidelines for Histologic Reporting

Subungual melanoma (SUM) is an uncommon variant of melanoma that is often difficult to diagnose, both clinically and pathologically. In an attempt to provide pathologic clues to diagnosis, especially in early lesions or small biopsies, and to provide practical advice to pathologists in reporting, the clinicopathologic features of 124 cases of SUM were reviewed, the largest series reported to date. The features of 28 cases of subungual melanoma in situ (MIS), comprising 4 cases of MIS and 24 cases where areas of MIS were present adjacent to dermal-invasive SUMs, were compared with those of a similar number of acral nevi to identify useful distinguishing features. The median age of the patients was 59 years and the most common site was the great toe (24%). Nine percent of cases were AJCC stage 0, 14% were stage I, 41% were stage II, 32% were stage III, and 4% were stage IV at initial diagnosis. The commonest histogenetic subtype was acral lentiginous (66%), followed by nodular (25%) and desmoplastic (7%). The majority of tumors were locally advanced at presentation with 79% being Clark level IV or V. The median Breslow thickness was 3.2u2009mm. The median mitotic rate was 3 per mm2 and 33% of cases demonstrated primary tumor ulceration. Seven of 29 patients (24%) who underwent a sentinel lymph node biopsy had nodal disease. Multivariate Cox-regression analysis showed higher disease stage to be the only significant predictor of shortened survival. In comparison to acral nevi, MIS more frequently showed lack of circumscription, a prominent lentiginous growth pattern, predominance of single cells over nests, moderate-to-severe cytologic atypia, a dense and haphazard pagetoid intraepidermal spread of melanocytes, and the presence of junctional/subjunctional lymphocytes (“tumor infiltrating lymphocytes”). Tumor infiltrating lymphocytes have not been highlighted previously as a feature of subungual MIS and represent a useful diagnostic clue. Guidelines for the reporting of SUMs are also presented. Knowledge and recognition of the pathologic features of SUMs and the important features that distinguish them from nevi should reduce the frequency of misdiagnosis.

Management of Merkel Cell Carcinoma: The Roles of Lymphoscintigraphy, Sentinel Lymph Node Biopsy and Adjuvant Radiotherapy

BackgroundMerkel cell carcinoma (MCC) is an uncommon, highly aggressive skin malignancy with a propensity to recur locally and regionally. However, its optimal treatment is uncertain. In this study, we aimed to assess the roles of lymphoscintigraphy and sentinel node (SN) biopsy, as well as radiotherapy, in the treatment of MCC.Patients and MethodsA retrospective analysis of 17 patients diagnosed with MCC (median age 74 years) over a 7-year period (median follow-up 16 months) was performed.ResultsOf 11 patients. 3 had a positive SN biopsy and, despite adjuvant radiotherapy, 2 of these 3 developed regional lymph node (RLN) recurrence. Of the remaining 8 patients who had a negative SN biopsy, however, 5 also had RLN recurrences. There were 9 patients who received adjuvant radiotherapy (RT) to the primary site, with no in-field recurrences; and 8 who received RT to their RLN field, with only 2 developing regional nodal recurrences—both were SN biopsy positive. During the follow-up period, 2 patients died, only 1 due to MCC.ConclusionThe results suggest that SN status may not be an accurate predictor of loco-regional recurrence in MCC. However, they strongly reinforce previous reports that radiotherapy, both locally and to regional nodes, provides effective infield disease control.

Desmoplastic Neurotropic Melanoma : A Clinicopathologic Analysis of 128 Cases

Several studies have suggested that desmoplastic neurotropic melanoma (DNM) is associated with higher local recurrence rates than other types of melanoma. The authors investigated the local recurrence rates for patients with DNM after surgery alone or surgery followed by radiotherapy (RT).